Thesis
The investigation of short structural variants in STMN2 (rs61386841), RAB27B (rs3060044), and ANKRD33B (rs55940283) for associations with sporadic amyotrophic lateral sclerosis
Honours, Murdoch University
2024
Abstract
Background and Objectives: Amyotrophic lateral sclerosis (ALS) is the most common adult motor neuron disease. About 90% of ALS cases are sporadic (sALS) and have no familial history of the disease. Despite heritability estimates of ~60% in sALS, disease linked genetic variants are only observed in about 10% of sALS patients. Thus, a large gap exists between the known and true genetic variability underlying sALS, referred to as missing heritability. Short structural variants (SSVs) have been suggested as potential markers of sALS disease risk and phenotypes addressing the missing heritability.
Methods: Our lab previously investigated SSVs in STMN2 (rs61386841), RAB27B (rs3060044), and ANKRD33B (rs55940283) for associations with sALS risk and age of onset. Here these SSVs were genotyped in a large cohort of Australian sALS patients using capillary electrophoresis. Utilising binary logistic regression and generalised linear models’ a case-control association study was conducted to assess SSVs’ association with sALS risk and age of onset.
Results: The previously observed associations between STMN2 (rs61386841) and sALS risk and age of onset was not extended here. ANKRD33B (rs55940283), also did not indicate an association with sALS risk or age of onset. RAB27B (rs3060044), however, showed a significant association with sALS disease risk in a sex specific manner, though this SSV was not associated with age of onset.
Conclusion: This study indicated associations between the RAB27B SSV and sALS risk in a sex-specific manner, suggesting its potential as a genetic stratification tool. While the STMN2 results weren't replicated, they align with other published studies. The research highlights the complexity of sALS genetics, emphasizes the importance of demographic factors, and contributes to improving patient stratification for clinical trials and targeted therapies.
Details
- Title
- The investigation of short structural variants in STMN2 (rs61386841), RAB27B (rs3060044), and ANKRD33B (rs55940283) for associations with sporadic amyotrophic lateral sclerosis
- Authors/Creators
- Noyan Nemati
- Contributors
- Anthony Akkari (Supervisor) - Murdoch University, Personalised Medicine CentreFrances Theunissen (Supervisor)Rita Mejzini (Supervisor) - Murdoch University, Centre for Molecular Medicine and Innovative Therapeutics
- Awarding Institution
- Murdoch University; Honours
- Identifiers
- 991005732483507891
- Murdoch Affiliation
- School of Medical, Molecular and Forensic Sciences
- Resource Type
- Thesis
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